Acknowledgement of Alport Syndrome has not been added yet.

Alport Syndrome affects nearly 1 in every 50,000 births worldwide, and it is estimated that about 30,000-60,000 people in the United States are diagnosed with this condition. Alport Syndrome is estimated to be responsible for 3% of kidney failures in children. 

 

There are three genetic types of Alport Syndrome, and, depending on the type, men and women are affected differently. In the XLAS type, or the X-Linked Alport Syndrome (the gene responsible is on the X-chromosome), males are affected more often than females. However, in the autosomal forms of the condition, both genders are affected with the same severity. The most common Alport Syndrome condition is X-Linked Alport Syndrome (XLAS).

Synonyms for Alport Syndrome has not been added yet.

Alport Syndrome is a genetic condition that is caused by DNA mutations in the COL4A5 gene, which is located on the X chromosome, or the COL4A3 and the COL4A4 genes, which are found on chromosome 2. 

 

X-Linked Alport Syndrome (XLAS) arises from a mutation in the COL4A5 gene in the X sex chromosome. Since males (with sex chromosomes X and Y) only have one X chromosome, it is far more common for males to develop XLAS compared to females who have 2 copies of the X sex chromosome. 

 

On the other hand, the autosomal (affecting one of the 22 pairs of non-sex chromosomes) types of Alport Syndrome involve the COL4A3 or the COL4A4 genes located on chromosome 2. Dominant genetic disorders present themselves when only one copy of the disease-causing variant is inherited, while recessive genetic disorders must have disease-causing variants on both of the copies in order for the individual to develop that particular condition. Accordingly, autosomal recessive Alport Syndrome arises when both copies of either the COL4A3 or the COL4A4 genes have disease-causing mutations, and dominant Alport Syndrome arises from a disease-causing mutation in only one copy of either the COL4A3 gene or the COL4A4 gene on chromosome 2. The risk of developing these autosomal types of Alport Syndrome is the same for males and females.

The COL4A3, COL4A4, and COL4A5 genes that are involved in Alport Syndrome encode  proteins called alpha chains of collagen IV. This is a key protein family that gives structural integrity to basement membranes, specifically those of the kidneys, ears and eyes. Basement membranes are sheets of protein that are responsible for providing structural support to the body’s organs. With mutations to these genes, progressive damage to the basement membranes occurs and the individual begins to exhibit the classic symptoms of Alport Syndrome. In particular, the kidney requires a strong basement membrane as it makes up the glomeruli, which are the small blood vessels that filter waste products from the blood and secrete them as urine. With abnormal collagen levels, the glomeruli often allow blood to leak into the urine, which is one of the major indicators of Alport Syndrome. In addition, the ears and eyes require this collagen to maintain their functioning, as well. Therefore, abnormal collagen causes hearing loss and can change the shape of the retina and lens leading to blindness.

The symptoms of Alport Syndrome generally begin in childhood and involve indications of kidney dysfunction, hearing loss, and eye alterations/abnormalities. Signs of kidney dysfunction include the presence of blood in an individual’s urine (hematuria) or protein in the urine (proteinuria). Over time, swelling and joint weakening/pain will become apparent. This will ultimately lead to end-stage renal disease if action is not taken. Individuals with Alport Syndrome may also experience sensorineural hearing loss, which is a form of hearing loss that affects the inner ear. Therefore, by the age of around 40, most affected individuals are almost completely deaf. In addition, the condition causes changes to the eye including abnormal coloration of the retina, transformation of the lens to cone-shaped, and damage to the macula (a region of the retina that allows for central vision). Together, these changes to the eye often result in vision loss. 

Alport Syndrome is generally diagnosed based on family history and after the individual displays certain characteristic symptoms of the condition. For example, early hearing loss or sudden kidney failure often indicate Alport Syndrome. From that point, doctors will conduct diagnostic tests including genetic testing, kidney biopsies, and ophthalmologic exams in order to confirm their diagnosis. 

 

Tests to confirm Alport Syndrome diagnosis include:

• Genetic testing → uses the techniques of next generation or whole exome sequencing

• Kidney biopsies → tissue specimen study that can be used to determine abnormalities in the collagen protein and glomerular basement membrane (GBM)

• Urinalysis → analysis of the urine to determine the prevalence of blood or protein in the urine

• Audiometry exam → testing hearing since the condition is often accompanied by hearing loss

• Ophthalmologic exams → testing vision since the condition is often accompanied by vision loss

• Doctor may advise other tests, such as blood and urine tests, in order to eliminate the possibility of other conditions that present themselves in similar ways

Although there is no cure for the condition, there are some forms of treatment for Alport Syndrome that generally involve monitoring and managing symptoms. Hearing aids are often used to combat hearing loss. In addition, medications such as angiotensin-converting enzyme (ACE) inhibitors have been used to improve kidney function in affected individuals. These medications prevent the production of angiotensin II, a chemical that narrows blood vessels, causing blood pressure to rise. Inhibiting this enzyme has shown to slow the progression of kidney disease, helping delay renal failure. For individuals that do not respond to ACE inhibitors, angiotensin receptor blockers (ARBs) can be used to stop angiotensin II from binding to receptors on blood vessels. Both ARBs and ACE inhibitors are commonly used in cases where proteinuria (protein in the urine) is present. Eventually, as the kidneys weaken, kidney transplants and/or dialysis are often the solution. 

 

The rate of Alport Syndrome progression varies across individuals and is difficult to predict. The prognosis for this condition depends on gender especially. Females affected by Alport Syndrome generally have a normal lifespan as they only experience some mild symptoms of the condition such as hematuria (presence of blood in urine). Alport Syndrome is more severe in males, and most male individuals with the condition will have end-stage renal disease and possibly deafness by around the age of 40.

Tips or Suggestions of Alport Syndrome has not been added yet.

“Alport Syndrome.” Genetic and Rare Diseases Information Center, U.S. Department of Health and Human Services, rarediseases.info.nih.gov/diseases/5785/alport-syndrome.  

“Alport Syndrome.” NORD (National Organization for Rare Disorders), 7 Apr. 2020, rarediseases.org/rare-diseases/alport-syndrome/.  

Russell, Julie. “Alport Syndrome Life Expectancy.” Alport Syndrome News, 12 Sept. 2018, alportsyndromenews.com/alport-syndrome-life-expectancy/#:~:text=Prognosis,arise%20as%20complications%20during%20pregnancy.   

“Alport Syndrome” National Kidney Foundation (2017). https://www.kidney.org/atoz/content/alport

“Alport Syndrome Medical Encyclopedia” NIH U.S. National Library of Medicine – MedlinePlus (2018). https://medlineplus.gov/ency/article/000504.htm

“Alport Syndrome” NIH U.S. National Library of Medicine (2018).  https://ghr.nlm.nih.gov/condition/alport-syndrome#synonyms

“Alport Syndrome – Patient Information.” Rare Renal – Information on rare kidney disease (2018) http://rarerenal.org/patient-information/alport-syndrome/

Kashtan, CE. “Alport Syndrome and Thin Basement Membrane Nephropathy” GeneReviews (2001). https://www.ncbi.nlm.nih.gov/books/NBK1207/